In the June 2012 issue of Biosecurity and Bioterrorism, Toner et al correctly note that H5N1 presents an ongoing pandemic threat in humans, and they warn that existing seroepidemiologic surveys that show a low prevalence of previous asymptomatic H5N1 infection in the human population are insufficient to conclude that such benign outcomes of infection are, in fact, common.
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As we continue to gather data on the distribution and prevalence of human H5N1 infections, it may be important to note that peak titers after H5N1 infection occur at about 4 to 6 weeks postinfection and may drop by as much as 32-fold over the course of a year,
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probably decreasing the sensitivity of serologic testing for past asymptomatic infections. Microneutralization testing may be more sensitive. Further, there is additional recent data that add, albeit marginally, to the corpus of information suggesting that an asymptomatic or very benign course after infection, while uncommon, is probably much more common than severe disease. For example, Kwon et al evaluated H5N1 antibodies in poultry workers in South Korea,
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and while rare—with only 9 of approximately 2,500 subjects positive for antibody response to H5N1—it is important to note that no illness was reported in this small subgroup. Perhaps of greater significance, the positive responders had demonstrated microneutralization titers, which are also generally believed to be much more specific for infection with a given subtype of influenza than assays based on hemagglutination testing. One can anticipate additional serological surveys that will better inform public health practitioners of the threat to humans from circulating H5N1 clades.
There are probably several mechanisms that explain infection without disease in individuals exposed to H5N1. Heterosubtypic immunity via both cross-reactive anti-H5 and anti-N1 antibodies from previous influenza infections or vaccination may also be operative,
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along with well-recognized but as yet poorly characterized T-cell responses, as noted by Toner and others.
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None of this is to suggest that the public health community should be complacent regarding novel influenza subtypes, as future mutations favoring human-to-human transmission and reassortment events leading to novel infectious variants are likely to occur. However, morbidity from novel influenza strains does not equate with an impending pandemic, let alone one with high mortality. It would appear likely that a systematic, prospective cohort study is in order to adequately capture the frequency of asymptomatic infection.
